Objective:To explore the pathogenic mechanism of a child with Waardenburg syndrome type 4C due to a c. 661_664dup (p.P222Lfs*60) variant of SOX10 gene through in vitro experiments. Methods:A child diagnosed at the Handan First Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, trio-whole exome sequencing was carried out. Pathogenicity of candidate variant was determined by bioinformatic analysis and reference to the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was verified by Sanger sequencing. Expression plasmids of wild-type SOX10 and the c. 661_664dup (p.P222Lfs*60) variant were constructed and transiently transfected into 293T cells to determine the expression at the RNA and protein levels. The 293T cells transiently transfected with the wild-type/mutant SOX10 were treated with 10 μg/mL cycloheximide (CHX) for 0, 4, 8, 24 h, respectively, and the degradation rate of target protein was detected by Western blotting assay. This study has been approved by the Ethics Committe of Handan First Hospital(Ethics No.HDYY-LW-25053). Results:The child was found to harbor a heterozygous c. 661_664dup (p.P222Lfs*60) variant of the SOX10 gene, which was unreported previously. The variant did not significantly alter the expression of SOX10 at the mRNA level but the protein level. After the CHX treatment, the degradation of mutant SOX10 protein had slowed down. Conclusion:The mutant SOX10 may affect the expression of downstream genes by affecting the degradation rate of its protein product.

Objective To explore the application effect of foot massage based on the brain-gut axis theory in patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,and to provide references for improving patients' sleep quality and gastrointestinal symptoms.Methods A total of 88 patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,who were treated at a Blood Purification Center of a tertiary-A general hospital in Hangzhou,Zhejiang Province from April to September 2024,were selected as a study subjects.They were randomly divided into an experimental group and a control group using the random number table method,with 44 cases in each group.The experimental group received foot massage based on the guidance of the brain-gut axis theory in addition to conventional treatment and nursing care,while the control group received conventional treatment and nursing care only.The intervention lasted for 3 months.The differences in the Pittsburgh Sleep Quality Index(PSQI)scores,Gastrointestinal Symptom Rating Scale(GSRS)scores,traditional Chinese medicine(TCM)syndrome scores,and serum 5-hydroxytryptamine and melatonin levels between the 2 groups before and after the intervention were compared.Results During the study period,no cases were lost in the experimental group,while 5 cases were lost in the control group.Ultimately,44 cases were included in the experimental group and 39 cases in the control group.After the intervention,the PSQI scores,GSRS scores,and TCM syndrome scores in both groups were lower than those before the intervention,and those in the experimental group were lower than those in the control group.The serum 5-hydroxytryptamine and melatonin levels were higher than those before the intervention,and the levels in the experimental group were higher than those in the control group,with statistically significant differences(all P＜0.001).Conclusion Foot massage based on the brain-gut axis theory can improve gastrointestinal symptoms and TCM syndromes in patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,and enhance their sleep quality.

OBJECTIVE: To explore the pathogenic mechanism of a child with Waardenburg syndrome type 4C due to a c.661_664dup (p.P222Lfs*60) variant of SOX10 gene through in vitro experiments. METHODS: A child diagnosed at the Handan First Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, trio-whole exome sequencing was carried out. Pathogenicity of candidate variant was determined by bioinformatic analysis and reference to the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was verified by Sanger sequencing. Expression plasmids of wild-type SOX10 and the c.661_664dup (p.P222Lfs*60) variant were constructed and transiently transfected into 293T cells to determine the expression at the RNA and protein levels. The 293T cells transiently transfected with the wild-type/mutant SOX10 were treated with 10 ug/mL cycloheximide (CHX) for 0, 4, 8, 24 h, respectively, and the degradation rate of target protein was detected by Western blotting assay. This study has been approved by the Ethics Committee of Handan First Hospital (Ethics No. HDYY-LW-25053). RESULTS: The child was found to harbor a heterozygous c.661_664dup (p.P222Lfs*60) variant of the SOX10 gene, which was unreported previously. The variant did not significantly alter the expression of SOX10 at the mRNA level but the protein level. After the CHX treatment, the degradation of mutant SOX10 protein had slowed down. CONCLUSION The mutant SOX10 may affect the expression of downstream genes by affecting the degradation rate of its protein product.
Humans ; HEK293 Cells ; Mutation ; SOXE Transcription Factors/metabolism* ; Waardenburg Syndrome/genetics* ; Child

Objective To explore the application effect of foot massage based on the brain-gut axis theory in patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,and to provide references for improving patients' sleep quality and gastrointestinal symptoms.Methods A total of 88 patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,who were treated at a Blood Purification Center of a tertiary-A general hospital in Hangzhou,Zhejiang Province from April to September 2024,were selected as a study subjects.They were randomly divided into an experimental group and a control group using the random number table method,with 44 cases in each group.The experimental group received foot massage based on the guidance of the brain-gut axis theory in addition to conventional treatment and nursing care,while the control group received conventional treatment and nursing care only.The intervention lasted for 3 months.The differences in the Pittsburgh Sleep Quality Index(PSQI)scores,Gastrointestinal Symptom Rating Scale(GSRS)scores,traditional Chinese medicine(TCM)syndrome scores,and serum 5-hydroxytryptamine and melatonin levels between the 2 groups before and after the intervention were compared.Results During the study period,no cases were lost in the experimental group,while 5 cases were lost in the control group.Ultimately,44 cases were included in the experimental group and 39 cases in the control group.After the intervention,the PSQI scores,GSRS scores,and TCM syndrome scores in both groups were lower than those before the intervention,and those in the experimental group were lower than those in the control group.The serum 5-hydroxytryptamine and melatonin levels were higher than those before the intervention,and the levels in the experimental group were higher than those in the control group,with statistically significant differences(all P＜0.001).Conclusion Foot massage based on the brain-gut axis theory can improve gastrointestinal symptoms and TCM syndromes in patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,and enhance their sleep quality.

Objective:To explore the pathogenic mechanism of a child with Waardenburg syndrome type 4C due to a c. 661_664dup (p.P222Lfs*60) variant of SOX10 gene through in vitro experiments. Methods:A child diagnosed at the Handan First Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, trio-whole exome sequencing was carried out. Pathogenicity of candidate variant was determined by bioinformatic analysis and reference to the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was verified by Sanger sequencing. Expression plasmids of wild-type SOX10 and the c. 661_664dup (p.P222Lfs*60) variant were constructed and transiently transfected into 293T cells to determine the expression at the RNA and protein levels. The 293T cells transiently transfected with the wild-type/mutant SOX10 were treated with 10 μg/mL cycloheximide (CHX) for 0, 4, 8, 24 h, respectively, and the degradation rate of target protein was detected by Western blotting assay. This study has been approved by the Ethics Committe of Handan First Hospital(Ethics No.HDYY-LW-25053). Results:The child was found to harbor a heterozygous c. 661_664dup (p.P222Lfs*60) variant of the SOX10 gene, which was unreported previously. The variant did not significantly alter the expression of SOX10 at the mRNA level but the protein level. After the CHX treatment, the degradation of mutant SOX10 protein had slowed down. Conclusion:The mutant SOX10 may affect the expression of downstream genes by affecting the degradation rate of its protein product.

Objective To mine the adverse drug events(ADE)signal of avatrombopag,an effective drug for thrombocytopenia treatment,based on real world data in order to provide reference for its clinical safety application.Methods The OpenVigil2.1 pharmacovigilance platform was used to obtain the ADE report data of avatrombopag from May 2018 to March 2023 in the database of FDA adverse event reporting system(FAERS).The ADE signals were classified and described by the system organ class(SOC)and preferred term(PT)of the ADE terminology set in the Medical Dictionary for Regulatory Activities(MedDRA),and reporting odds ratio(ROR)and UK Medicines and Healthcare Products Regulatory Agency(MHRA)comprehensive standard were used to detect the positive ADE signals.Results A total of 1 879 ADE reports related to avatrombopag were obtained,24 SOCs were involved,and 28 positive ADE signals were detected at PT level.Among these signals,the strongest ones were renal vein thrombosis,portal vein thrombosis and graft versus host disease,while the reports accounting for the largest numbers were headache,fatigue and asthenia.There were 8 ADE signals discovered newly,that is,seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea.Conclusion For clinical use of avatrombopag,clinicians should not only concern the risk of thrombosis,but also pay close attention to ADE signals such as seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea that are not documented in the instructions.

Thyroid cancer is the most common malignant tumor of the head and neck, among which papillary thyroid carcinoma is the most common. Papillary thyroid carcinoma with a diameter of ≤ 1.0 cm is called thyroid micropapillary carcinoma. In recent years, thermal ablation technology for the treatment of thyroid micropapillary carcinoma has developed rapidly at home and abroad. At present, many guidelines, consensus and clinical studies related to thermal ablation treatment of thyroid micropapillary carcinoma have been published at home and abroad. Based on the existing literature, guidelines and clinical studies, this article summarizes, discusses and analyzes the advantages, indications, efficacy, safety, and existing problems of thermal ablation therapy for thyroid cancer.

Objective:To summarize the clinical features and pregnancy outcomes of fetal micrognathia.Methods:This retrospective study enrolled 52 cases of fetal micrognathia diagnosed at Shandong Provincial Maternal and Child Health Hospital Affiliated to Qingdao University and Affiliated Maternity and Child Health Care Hospital of Nantong University from January 2014 to December 2022. Clinical features, genetic testing results, and pregnancy outcomes of the cases were summarized. These cases were divided into two groups based on whether they were complicated by other system anomalies: non-isolated micrognathia (49 cases) and isolated micrognathia (three cases). The non-isolated micrognathia cases were further divided into two subgroups: cleft palate group (21 cases) and non-cleft palate group (28 cases). Clinical features were compared between different groups. Statistical analysis was performed using two independent samples t-test, Chi-square test, or Fisher's exact test. Results:(1) The non-isolated micrognathia cases were complicated by one to six system anomalies, with the most common being facial anomalies (59.2%, 29/49), followed by circulatory system (51.0%, 25/49), musculoskeletal system (44.9%, 22/49), nervous system (34.7%, 17/49), digestive system (12.2%, 6/49), and urinary system anomalies (8.2%, 4/49). (2) Among 52 cases, nine non-isolated micrognathia cases received genetic testing, and the results indicated six with genetic abnormalities. (3) Forty-seven cases chose to terminate the pregnancies, while the other five cases continued the pregnancies (all fetuses were non-isolated micrognathia) and resulted in live births. Treatment was withdrawn in one live birth due to multiple anomalies, and the other four neonates required mechanical ventilation (two died after withdrawal of treatment; two underwent surgeries after birth and the prognosis of them was good during a one-year outpatient follow-up). (4) The proportion of women with polyhydramnios [28.6% (6/21) vs. 3.6% (1/28), Fisher's exact test, P=0.033] and the proportion of fetuses with confirmed Pierre Robin sequence [85.7% (18/21) vs. 7.1% (2/28), Fisher's exact test, P<0.001] were higher in the cleft palate group than those in the non-cleft palate group. Conclusions:Fetal micrognathia cases revealed by prenatal ultrasound should undergo a comprehensive screening for other system anomalies, especially cleft palate. Fetuses with micrognathia and multiple system anomalies often have a poor prognosis. Besides, it is recommended to take genetic testing. For fetuses with micrognathia, preparations for neonatal resuscitation at birth are essential to avoid adverse outcomes due to breathing difficulties.

Objective: To explore the bidirectional correlation between daily physical activity and different emotional states of university students with sports major, and to provide theoretical basis for promoting equality between physical and mental health of college students. Methods: The accelerometer and daily emotion scale were used to evaluate 219 physical education major college students recruited from Tianjin University of Sport. Correlation analysis, intra group correlation coefficient analysis and Harman single factor method were used to test the data, and Mplus 7.4 was used to analyze cross hysteria. Results: Physical activity was positively correlated with high arousal/low arousal positive emotion, and negatively correlated with low arousal/high arousal negative emotion ( r=0.94, 0.63, -0.28, -0.17, P <0.05). The cross lag model showed that physical activity on Thursday and Friday positively predicted high arousal positive emotion on Friday and Saturday, and high arousal positive emotion on Thursday and Friday positively predicted physical activity on Friday and Saturday( β =0.91, 0.20; 0.88, 0.39, P ＜0.05). Low arousal positive emotion on Thursday and Friday was a positive prediction of physical activity on Friday and Saturday, but only physical activity on Thursday positively predicted low arousal positive emotion on Friday( β=0.68, 0.35, 0.70, P ＜0.05). Low arousal negative emotion on Thursdays and Fridays negatively predicted physical activity on Friand and Saturdays( β=-0.37, -0.40, P ＜0.05). Conclusion There is a bidirectional correlation between daily physical activity and positive emotion, but a weak correlation with negative emotion. Attention should be paid to the emotional benefits of physical activity and the increasing physical activity by greater mood improvements.

Abstract：Objective To evaluate the basic development status of public health emergencies of infectious diseases in Hainan Province from 2013 to 2022, analyze the distribution and characteristics of these emergencies, as to provide important scientific basis for the study and formulation of economic health development planning policies, for the health security policies and infectious disease prevention and control strategies in Hainan Province. Methods The relevant statistical data of public health emergencies involving infectious diseases reported in Hainan Province from 2013 to 2022 were collected, and the status quo of these emergencies was analyzed by using descriptive data statistical analysis method. The ARIMA model was used to predict the number of public health emergencies reported by infectious diseases in Hainan Province from 2023 to 2025. Results From 2013 to 2022, a total of 482 public health emergencies were reported in Hainan Province, of which 426 were infectious disease public health emergencies, accounting for 88.38%, with a total of 8 876 cases, an incidence rate of 0.61%, and eight deaths, a case fatality rate of 0.09%. The major public health emergencies of infectious diseases were unclassified events and general events, accounting for 69.25% and 29.58%, respectively. The main diseases were novel coronavirus infection, chickenpox and hand, foot and mouth disease, accounting for 45.07%, 15.49% and 11.97%, respectively; in terms of time distribution, the number of reported incidents showed an upward trend over time, with a decline in 2021, and mainly had three peak periods, April, August and December, with a total of 220 cases reported; in terms of regional distribution, the major cities and counties reported were Haikou, Wanning and Wenchang, accounting for 27.46%, 19.25% and 9.86%, respectively; in terms of location distribution, the events mainly occurred in schools, accounting for 42.02% of the total number of incidents. The ARIMA(1, 1, 0) model was used to predict infectious disease public health emergencies, and the results showed that the forecast state would be stable from 2023 to 2025, with no obvious upward trend, that is, the fluctuation range of public health emergencies related to infectious diseases in Hainan Province would be stable in the next three years. Conclusion The number of infectious disease public health emergencies reported in Hainan Province from 2013 to 2022 has increased year by year, with a decline in 2021. Although the forecast shows that public health emergencies such as infectious diseases are relatively stable with no obvious upward trend, the prevention and control of the epidemic should not be taken lightly. Hainan Province should continue to increase the investment in monitoring public health emergencies, improve the information system of public disease prevention and control, and carry out real-time monitoring of public health emergencies of infectious diseases.